Expression and Genetic Loss of Function Analysis of the HAT/DESC Cluster Proteases TMPRSS11A and HAT

Genome mining at the turn of the millennium uncovered a new family of type II transmembrane serine proteases (TTSPs) that comprises 17 members in humans and 19 in mice. TTSPs phylogenetically belong to one of four subfamilies: matriptase, hepsin/TMPRSS, corin and HAT/DESC. Whereas a wealth of information now has been gathered as to the physiological functions of members of the hepsin/TMPRSS, matriptase, and corin subfamilies of TTSPs, comparatively little is known about the functions of the HAT/DESC subfamily of proteases. Here we perform a combined expression and functional analysis of this TTSP subfamily. We show that the five human and seven murine HAT/DESC proteases are coordinately expressed, suggesting a level of functional redundancy. We also perform a comprehensive phenotypic analysis of mice deficient in two of the most widely expressed HAT/DESC proteases, TMPRSS11A and HAT, and show that the two proteases are dispensable for development, health, and long-term survival in the absence of external challenges or additional genetic deficits. Our comprehensive expression analysis and generation of TMPRSS11A- and HAT-deficient mutant mouse strains provide a valuable resource for the scientific community for further exploration of the HAT/DESC subfamily proteases in physiological and pathological processes.

• Publication year

  2011

• Venue

  PLoS ONE

• Publication date

  2011-08-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0023261PMID 21853097PMCID 3154331
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Explorer A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo

  2016cited by this paper
• Membrane-Anchored Serine Proteases in Health and Disease

  2011cited by this paper
• Membrane-anchored serine proteases in vertebrate cell and developmental biology.

  2011cited by this paper
• A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo

  2011cited by this paper
• Tmprss3, a Transmembrane Serine Protease Deficient in Human DFNB8/10 Deafness, Is Critical for Cochlear Hair Cell Survival at the Onset of Hearing*

  2011cited by this paper
• Local protease signaling contributes to neural tube closure in the mouse embryo.

  2010cited by this paper
• Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases

  2010cited by this paper
• Enteropeptidase, a type II transmembrane serine protease.

  2009cited by this paper
• Type II Transmembrane Serine Proteases*

  2009cited by this paper
• Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)

  2008cited by this paper
• An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss

  2008cited by this paper
• Neurobin/TMPRSS11c, a novel type II transmembrane serine protease that cleaves fibroblast growth factor-2 in vitro.

  2008cited by this paper
• The Degradome database: mammalian proteases and diseases of proteolysis

  2008cited by this paper
• Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis.

  2008cited by this paper
• Type II transmembrane serine proteases in development and disease.

  2008cited by this paper
• The Serine Protease TMPRSS6 Is Required to Sense Iron Deficiency

  2008cited by this paper
• Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase.

  2007cited by this paper
• The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions.

  2007cited by this paper
• Mice deficient for the type II transmembrane serine protease, TMPRSS1/hepsin, exhibit profound hearing loss.

  2007cited by this paper
• The serine protease Corin is a novel modifier of the agouti pathway

  2007cited by this paper
• Human airway trypsin-like protease stimulates human bronchial fibroblast proliferation in a protease-activated receptor-2-dependent pathway.

  2006cited by this paper
• Phenotypic Analysis of Mice Lacking the Tmprss2-Encoded Protease

  2006cited by this paper
• Human airway trypsin‐like protease induces amphiregulin release through a mechanism involving protease‐activated receptor‐2‐mediated ERK activation and TNF α‐converting enzyme activity in airway epithelial cells

  2005cited by this paper
• Corin Gene Minor Allele Defined by 2 Missense Mutations Is Common in Blacks and Associated With High Blood Pressure and Hypertension

  2005cited by this paper
• Hypertension in mice lacking the proatrial natriuretic peptide convertase corin.

  2005cited by this paper
• Mouse DESC1 Is Located within a Cluster of Seven DESC1-like Genes and Encodes a Type II Transmembrane Serine Protease That Forms Serpin Inhibitory Complexes*

  2004cited by this paper
• The adrenal secretory serine protease AsP is a short secretory isoform of the transmembrane airway trypsin-like protease.

  2004cited by this paper
• Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.

  2004cited by this paper
• Mutagenic Insertion and Chromosome Engineering Resource (MICER)

  2004cited by this paper
• Type II transmembrane serine proteases

  2003cited by this paper
• Human and mouse proteases: a comparative genomic approach

  2003cited by this paper
• Membrane anchored serine proteases: A rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer

  2003cited by this paper
• Type II transmembrane serine proteases.

  2003cited by this paper
• Processing of Pro-atrial Natriuretic Peptide by Corin in Cardiac Myocytes*

  2002cited by this paper
• Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis

  2002cited by this paper
• Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency.

  2002cited by this paper
• Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness

  2001cited by this paper
• Type II Transmembrane Serine Proteases

  2001cited by this paper
• Characterization of a Serine Protease that Cleaves Pro- -Melanotropin at the Adrenal to Stimulate Growth

  2001cited by this paper
• Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck

  2001cited by this paper
• Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness

  2001cited by this paper
• Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme.

  2000cited by this paper
• Type II Transmembrane Serine Proteases INSIGHTS INTO AN EMERGING CLASS OF CELL SURFACE PROTEOLYTIC ENZYMES*

  2000cited by this paper
• Cloning and Characterization of the cDNA for Human Airway Trypsin-like Protease*

  1998cited by this paper
• Fibrinogenolytic activity of a novel trypsin-like enzyme found in human airway.

  1998cited by this paper
• Purification, characterization, and localization of a novel trypsin-like protease found in the human airway.

  1997cited by this paper
• Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.

  1993cited by this paper
• ‡Address correspondence to:

  year unknowncited by this paper

• Host-derived protease promotes aggregation of Staphylococcus aureus by cleaving the surface protein SasG

  2024cites this paper
• Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function

  2023cites this paper
• TMPRSS11D/ALR-mediated ER stress regulates the function of myeloid-derived suppressor cells in the cervical cancer microenvironment.

  2023cites this paper
• Bone morphogenetic protein 2- and estradiol-17β-induced changes in ovarian transcriptome during primordial follicle formation

  2022influential citation
• Elevated expression of the membrane-anchored serine protease TMPRSS11E in NSCLC progression.

  2022cites this paper
• Multifactorial Traits of SARS-CoV-2 Cell Entry Related to Diverse Host Proteases and Proteins

  2021influential citation
• TMPRSS11a is a novel age‐altered, tissue specific regulator of migration and wound healing

  2021cites this paper
• Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2

  2021cites this paper
• Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease

  2020cites this paper
• Membrane-anchored serine proteases as regulators of epithelial function.

  2020cites this paper
• Targeting Crucial Host Factors of SARS-CoV-2

  2020cites this paper
• Identify differential gene expressions in fatty infiltration process in rotator cuff

  2019cites this paper
• Activation of Viruses by Host Proteases

  2019cites this paper
• Iterative, multiplexed CRISPR-mediated gene editing for functional analysis of complex protease gene clusters

  2019influential citation
• Human airway trypsin-like protease enhances interleukin-8 synthesis in bronchial epithelial cells by activating protease-activated receptor 2.

  2019cites this paper
• Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth

  2019cites this paper
• The testis-specific serine proteases PRSS44, PRSS46, and PRSS54 are dispensable for male mouse fertility

  2019cites this paper
• Membrane-Anchored Serine Proteases: Host Cell Factors in Proteolytic Activation of Viral Glycoproteins

  2018cites this paper
• Activation of the Hemagglutinin of Influenza Viruses

  2018cites this paper
• TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1

  2018cites this paper
• Human airway trypsin-like protease (HAT) is released into saliva.

  2018cites this paper
• High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer

  2017cites this paper
• Human airway trypsin-like protease, a serine protease involved in respiratory diseases.

  2017cites this paper
• The Transmembrane Serine Protease HAT-like 4 Is Important for Epidermal Barrier Function to Prevent Body Fluid Loss

  2017cites this paper
• Type II transmembrane serine proteases as potential target for anti-influenza drug discovery

  2017cites this paper
• Airway proteases: an emerging drug target for influenza and other respiratory virus infections

  2017cites this paper
• Cell Surface Human Airway Trypsin‐Like Protease Is Lost During Squamous Cell Carcinogenesis

  2016cites this paper
• The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases

  2016cites this paper
• Extracellular: Plasma Membrane Proteases – Serine Proteases

  2015cites this paper
• Studies on the host response to influenza A virus infections in mouse knock-out mutants

  2015cites this paper
• Coronavirus and Influenza Virus Proteolytic Priming Takes Place in Tetraspanin-Enriched Membrane Microdomains

  2015cites this paper
• The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity*

  2014cites this paper
• The hemagglutinin: a determinant of pathogenicity.

  2014cites this paper
• Functional Analysis of a Missense Mutation in the Serine Protease Inhibitor SPINT2 Associated with Congenital Sodium Diarrhea

  2014cites this paper
• Corin in Natriuretic Peptide Processing and Hypertension

  2014cites this paper
• DESC1 and MSPL Activate Influenza A Viruses and Emerging Coronaviruses for Host Cell Entry

  2014cites this paper
• Cleavage Specificity Analysis of Six Type II Transmembrane Serine Proteases (TTSPs) Using PICS with Proteome-Derived Peptide Libraries

  2014cites this paper
• HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers

  2014cites this paper
• TMPRSS2 Is a Host Factor That Is Essential for Pneumotropism and Pathogenicity of H7N9 Influenza A Virus in Mice

  2014cites this paper
• Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium

  2013cites this paper
• Activation of Influenza A Viruses by Host Proteases from Swine Airway Epithelium

  2013cites this paper
• Genetics of flystrike, dagginess and associated traits in New Zealand dual-purpose sheep : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand

  2013cites this paper
• Hemagglutinin activating host cell proteases provide promising drug targets for the treatment of influenza A and B virus infections.

  2012cites this paper